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Pineal gland once considered as rudimentary or vestigial, has become a principal endocrine gland that regulates the body’s internal environment, after the discovery of melatonin-a hormone produced by it. Melatonin is also synthesized from extrapineal sites such as retina, skin, platelets, bone marrow, and gastrointestinal tract. The chronobiological property of this hormone in maintaining the circadian rhythm by synchronizing with the dark-light cycle is well-established. Melatonin also possesses anti-inflammatory, anti-depressant, anti-oxidant, oncostatic, immunomodulatory, antiepileptic, and glucose-regulating properties. These pleiotropic effects of melatonin on diverse organ systems either through a receptor or non-receptor mediated pathways are under investigation. This review highlights the pathophysiological and pharmacological actions of melatonin along with melatonergic agonists in “real life” clinical practice.